17-7445140-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000747.3(CHRNB1):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,609,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000747.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.13G>A | p.Ala5Thr | missense_variant | Exon 1 of 11 | 1 | NM_000747.3 | ENSP00000304290.2 | ||
ENSG00000272884 | ENST00000575331.1 | n.4727G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 1 | |||||
CHRNB1 | ENST00000572857.5 | c.13G>A | p.Ala5Thr | missense_variant | Exon 1 of 6 | 4 | ENSP00000461402.1 | |||
CHRNB1 | ENST00000574054.1 | n.33G>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000853 AC: 2AN: 234396Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129518
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1456694Hom.: 0 Cov.: 31 AF XY: 0.00000828 AC XY: 6AN XY: 724632
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152382Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74520
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 2A Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 5 of the CHRNB1 protein (p.Ala5Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CHRNB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2038566). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Inborn genetic diseases Uncertain:1
The c.13G>A (p.A5T) alteration is located in exon 1 (coding exon 1) of the CHRNB1 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at